Finding new ways to improve yield and/or storage stability is of continued interest in the area of industrial polypeptide manufacture. It has been shown in both fungal and bacterial recombinant host cells that inactivation of one or more proteolytic enzyme, often by deleting the encoding gene(s), can lead to improved yield and/or storage stability.
However, there are also examples where the inactivation of a proteolytic enzyme in a host cell has had undesirable consequences for the host cell phenotype. One such example is the inactivation of the PepC protease in an Aspergillus fumigutus host, wherein the PepC inactivation was shown to reduce sporulation and growth rate significantly, as reported by Reichard U. et al. (2000, Int J Med Microbiol. 290, 549-558).
In the biotech industry it is very important that a fungal recombinant production host cell retains its ability to sporulate, in order to be able to make cell-bank preparations, a crucial requirement for consistent polypeptide manufacture.